Correlation between clinical phenotypes and X-inactivation patterns in six female carriers with heterozygote vasopressin type 2 receptor gene mutations

Endocr J. 2008 May;55(2):277-84. doi: 10.1507/endocrj.k07-083. Epub 2008 Mar 7.


About 90% of patients with congenital nephrogenic diabetes insipidus (NDI) have vasopressin type 2 receptor (V2R) gene mutations that are inherited in an X-linked recessive manner. Although most female carriers are asymptomatic, some female carriers show polydipsia and polyuria. The reason why female carriers show NDI symptoms is explained by skewed X-inactivation. We studied X-inactivation patterns of six female carriers with heterozygote V2R gene mutations. The X-inactivation pattern in peripheral blood leukocytes was examined using methylation analysis of the polymorphic CAG repeat in the androgen receptor gene. Two asymptomatic female carriers showed random X-inactivation (61.9% and 60.7%). Skewed X-inactivation patterns (71.6%, 79.4%, and 91.2%) occurring preferentially to normal X alleles were recognized in three female carriers who showed clinical NDI symptoms. However, in one female carrier who showed clinical NDI symptoms, random X-inactivation (55.4%) was recognized. In conclusion, the clinical NDI phenotypes may correlate with the X-inactivation patterns in female carriers with heterozygote V2R gene mutations. However, in some female carriers, we cannot predict the clinical phenotypes by the evaluation of the X-inactivation patterns in peripheral blood leukocytes, because X-inactivation ratios within an individual are sometimes different between tissues.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Child
  • Diabetes Insipidus, Nephrogenic / blood
  • Diabetes Insipidus, Nephrogenic / genetics*
  • Female
  • Genes, X-Linked / genetics
  • Heterozygote*
  • Humans
  • Infant
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Mutation / genetics*
  • Pedigree
  • Phenotype*
  • Receptors, Vasopressin / genetics*
  • Receptors, Vasopressin / metabolism
  • X Chromosome Inactivation / genetics*


  • Receptors, Vasopressin